Research

Upon infection, cytosolic sensors in the host cell recognize the incoming virus and stimulate the production of type I interferons (IFNs). The same or neighboring cell binds secreted IFNs and triggers JAK/STAT signaling pathway resulting in the expression of several hundreds of IFN-stimulated genes (ISGs). Some of these ISGs are antiviral effectors that target different steps of the viral life cycle. Others are regulators or the IFN pathway. A main focus of the Li Lab is to elucidate the mechanism of these ISGs by utilizing tissue culture systems and mouse models of viral infection. In the past, work on two ISGs, ZAP and IRF2, advances our understanding of host strategies that inhibit viral translation and promote viral clearance in the central nervous system.​

A genome-wide siRNA screening approach was used to identify co-factors required for ZAP-mediated inhibition of Sindbis virus. Among the candidate co-factors, TRIM25, an E3 ubiquitin ligase and an ISG, enhances ZAP’s antiviral activity. The Li Lab is currently studying the consequences of ubiquitination on TRIM25/ZAP synergy.

In contrast to the traditional cDNA overexpression screen, CRISPR-based activation strategy allows for upregulation of genes and isoforms, and non-coding RNAs from their endogenous promoters. By using this approach, the Li Lab is identifying novel host factors that are required for or inhibitory against emerging RNA viruses.

Mono- and poly-ADP-ribosylation of proteins by PARPs are important for a variety of nuclear processes, such as DNA repair, cell death and chromatin remodeling. However, the role of ADP-ribosylation in innate immune responses against viruses that replicate in the cytoplasm is underappreciated. The Li Lab is investigating the antiviral spectrum of some of these PARPs.